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Tisp40, a spermatid specific bZip transcription factor, functions by binding to the unfolded protein response element via the Rip pathway
Author(s) -
Nagamori Ippei,
Yabuta Norikazu,
Fujii Takayuki,
Tanaka Hiromitsu,
Yomogida Kentaro,
Nishimune Yoshitake,
Nojima Hiroshi
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00860.x
Subject(s) - biology , transcription factor , spermatid , microbiology and biotechnology , transmembrane protein , endoplasmic reticulum , transmembrane domain , biochemistry , gene , genetics , receptor , sperm
TISP40 , a mouse spermatid‐specific gene, encodes a CREB/CREM family transcription factor that is predominantly expressed during spermiogenesis. We report here that TISP40 generates two types of proteins, Tisp40α and Tisp40β, both of which contain a transmembrane domain and localize to the endoplasmic reticulum (ER). In contrast, mutant proteins lacking the transmembrane domain (Tisp40α/βΔTM) primarily localize to the nucleus. Endoglycosidase H treatment shows that the C‐terminus of Tisp40α/β is glycosylated. Protease experiments demonstrate that Tisp40α/β are Type II transmembrane proteins that are released into the nucleus by a two‐step cleavage mechanism called ‘regulated intramembrane proteolysis’ (Rip). Unlike previously published observations, Tisp40α does not bind to the NF‐κB site; instead, it specifically binds to the unfolded protein response element (UPRE). Luciferase assays reveal that Tisp40βΔTM activates transcription through UPRE. Northern blot analysis shows that Tisp40α/βΔTM proteins up‐regulate EDEM (ER degradation of enhancing α‐manosidase‐like protein) mRNA. These observations unveil a novel event in mouse spermiogenesis and show that the final stage of trans‐criptional regulation is controlled by the Rip pathway.